Gastric Cancer, Gastroesophageal Cancer, Metastatic Esophageal Cancer
Conditions
Brief summary
To estimate and compare the response rates in patients treated with mDCF based on methylation status of CHFR.
Detailed description
To estimate and compare the response rates in patients treated with mDCF based on methylation status of CHFR. The overall response rates in the un-methylated and methylated patient groups will be reported with a exact 95% binomial confidence interval. A chi-square test will be used for comparison.
Interventions
DRUGDocetaxel
Modified Docetaxel 40mg/m2 on Day 1
DRUGLeucovorin
Leucovorin 400mg/m2 on Day 1
DRUGFluorouracil
Fluorouracil 400mg/m2 on Day 1 Fluorouracil 1000mg/m2/day on Days 1 and 2
DRUGCisplatin
Cisplatin (or Carboplatin) 40mg/m2 on Day 3
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have metastatic disease of the esophagus, gastroesophageal junction or stomach. Patients with locally recurrent disease who are not deemed eligible for radiation are also permitted. * Histological, cytologic or radiographic documentation of metastatic adenocarcinoma or squamous cell carcinoma of the esophagus, gastroesophageal junction or stomach. Radiologic, endoscopic, histologic or cytologic evidence of locally recurrent disease is also permitted. * Patients must be untreated with chemotherapy for metastatic or locally recurrent disease. Prior radiation therapy is permitted. * Patients must have measurable disease as per RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease. * Age \>18 years and ≤ 80 years. * ECOG performance status \<2 (Karnofsky \>60%, see Appendix A). * Life expectancy of greater than 3 months. * Patients must have normal organ and marrow function. * Patients must not have any of the following conditions: * Recent major surgery, hormonal therapy (other than replacement) or chemotherapy, within 4 weeks prior to entering the study or those who have not recovered from the adverse events of treatment. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy on this trial. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. * Patients who are receiving any investigational agents. * Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy used in the study. * Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, or St John's Wort; these drugs induce CYP3A and may decrease levels of taxanes. 5-FU is a strong CYP2C9 inducer, and concomitant use with carvedilol, celecoxib, fosphenytoin, fluoxetine, phenytoin, warfarin and other CYP2C9 substrates should be used with caution. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study because chemotherapy has the potential for teratogenic or abortifacient effects. * HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with chemotherapeutic agents. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response | 4 months | Number of participants treated with mDCF with progressive disease (PD), stable disease (SD), partial response (PR), non-complete response and non-progressive disease (non-CR/non-PD), and partial response with progressive disease clinically (PR/PD) as defined by RECIST criteria. Response is compared based on CHFR-methylation status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CHFR Methylation Status | Baseline | Number of participants with advanced esophagogastric cancer that are CHFR-methylated or unmethylated at baseline. |
| Overall Survival | 2 Years | Number of participants alive at 2 years. |
Countries
United States
Participant flow
Pre-assignment details
6 subjects were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer Participants receive modified Docetaxel 40mg/m2, Leucovorin 400mg/m2 and Fluorouracil 400mg/m2 on day 1, Fluorouracil 1000mg/m2 per day on days 1 and 2 and Cisplatin 40mg/m2 (or Carboplatin) on day 3 in Patients With Metastatic Esophageal, Gastroesophageal And Gastric Cancer.
Docetaxel: Modified Docetaxel 40mg/m2 on Day 1
Leucovorin: Leucovorin 400mg/m2 on Day 1
Fluorouracil: Fluorouracil 400mg/m2 on Day 1 Fluorouracil 1000mg/m2/day on Days 1 and 2
Cisplatin: Cisplatin (or Carboplatin) 40mg/m2 on Day 3 | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Metastatic Esophageal, Gastroesophageal & Gastric Cancer |
|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 9.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 21 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 21 |
| other Total, other adverse events | 18 / 21 |
| serious Total, serious adverse events | 3 / 21 |
Outcome results
Primary
Response
Number of participants treated with mDCF with progressive disease (PD), stable disease (SD), partial response (PR), non-complete response and non-progressive disease (non-CR/non-PD), and partial response with progressive disease clinically (PR/PD) as defined by RECIST criteria. Response is compared based on CHFR-methylation status.
Time frame: 4 months
Population: Response could not be assessed in 2/21 participants since imaging was not evaluable, therefore RECIST reads could not be obtained.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | CHFR-methylated | PD | 3 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | CHFR-methylated | SD | 0 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | CHFR-methylated | PR | 2 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | CHFR-methylated | non-CR/non-PD | 0 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | CHFR-methylated | PR/PD | 1 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | CHFR-unmethylated | PD | 3 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | CHFR-unmethylated | SD | 3 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | CHFR-unmethylated | PR | 5 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | Unknown methylation status | PR/PD | 0 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | CHFR-unmethylated | non-CR/non-PD | 1 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | CHFR-unmethylated | PR/PD | 0 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | Unknown methylation status | PD | 0 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | Unknown methylation status | SD | 0 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | Unknown methylation status | PR | 1 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Response | Unknown methylation status | non-CR/non-PD | 0 Participants |
Secondary
CHFR Methylation Status
Number of participants with advanced esophagogastric cancer that are CHFR-methylated or unmethylated at baseline.
Time frame: Baseline
Population: Only 18/21 participants had evaluable data for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | CHFR Methylation Status | CHFR-methylated | 6 Participants |
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | CHFR Methylation Status | CHFR-unmethylated | 12 Participants |
Secondary
Overall Survival
Number of participants alive at 2 years.
Time frame: 2 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | Overall Survival | 2 Participants |